A unique animal system , damselfish, neurofibromatosis (DNF), will be used to address basic questions in the pathogenesis of neurofibromas, malignant peripheral nerve sheath tumors and chromatophoromas. Investigation of the mechanisms controlling alterations of Schwann cells, perineurial cells and axons during the development of peripheral nerve sheath tumors in humans could be greatly facilitated by the use of an animal model in which these tumors and the neoplastic process could be manipulated experimentally, both in vivo and in vitro. DNF is caused by an unusual, transmissible, virus-like agent, the damselfish-virus like agent (DVLA), and appears to be the only naturally occurring example of a transmissible tumor involving any neuroectodermally the only naturally occurring example of a transmissible tumor involving any neuroectodermally derived cell type. Thus, this model system provides a unique opportunity for experimental manipulation of this carcinogenic process at many levels. Ongoing research on DNF will address hypotheses relevant to a complete characterization of this agent and its relationship to neoplastic transformation of these neuroectodermal cell types through four interrelated aims: (1) The complete sequence and transcriptional pattern of DVLA will be documented and infectious clones of the DVLA genome will be created. (2) The status of DVLA replication in tumors and infected non-tumor cell types from diseased fish will be determined in vivo and in vitro. (3) Factors controlling replication, transcription, translation and production of infectious material in vitro will be identified by manipulating cell lines chronically infected with DVLA and developing infection assay systems. These systems will also be used to assess the tumorigenicity of isolates of this agent in vivo. (4) The full range of proteins expressed by DVLA will be identified and antibodies developed to selected viral proteins. The proposed studies should yield information on mechanisms of tumor development in the peripheral nervous system applicable to understanding these processes in human disorders such as neurofibromatosis type 1.